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dc.contributor.advisorErxleben, Andrea
dc.contributor.authorMacFhionnghaile, Pól
dc.description.abstractPolymorphic transformations are known to occur as a result of many factors, one of the most prominent being recrystallisation from different solutions. Though other factors have been known to induce polymorphic change, these can include environmental factors and mechanical/physical stress. During many manufacturing processes mechanical stress such as milling or compression can induce polymorphic transformation, as well as environmental effects during storage such as changes in temperature or humidity. In this body of work the solid state transformations of two model polymorphic drugs, sulfamerazine and sulfathiazole, were studied. For this accurate analytical methods were developed for comprehensive polymorphic analysis. Previous studies have shown the effects of mechanical stress on the solid state chemistry of sulfamerazine. It has already been shown that compression during tabletting can cause transformation from sulfamerazine form I (FI) to form II (FII), that cryo-milling can generate amorphous content, and milling at room temperature can transform FI to FII. In this work, methods to prepare bulk FII from FI were reviewed. Both forms I & II of sulfamerazine were monitored during milling at room temperature and low temperatures, achieving the first complete transformation to sulfamerazine's amorphous phase (FA). FA produced from cryo-milling both FI and FII at different time intervals were compared to determine the optimal method to prepare (FA) for multivariate analysis. This optimal method resulted in the most stable amorphous phase, while taking the least amount of time to prepare. FI, FII and FA were used to prepare binary and ternary mixtures for chemometric models using XRPD, NIR and IR spectroscopy. This gave a novel means to analysis and monitors the solid state transformations of sulfamerazine observed during the room temperature milling and cryo-milling of FI and FII. The shelf-life of FA was also monitored when stored under vacuum at 4oC and room temperature using these calibration models. For the work with sulfathiazole, low content analysis of different solid sates was used to determine the limitations of a number of analytical techniques such as XRPD, NIR and IR spectroscopy. The analytical method that produced the most accurate calibrations was used in other studies. For the first time the amorphous phase of sulfathiazole was prepared via cryo-milling forms I and III. These produced purer samples of the amorphous phase when compared to samples prepared by the melt quench method. With a successful method to prepare pure samples of the amorphous phase, novel ternary studies containing the amorphous phase of sulfathiazole, and form I and form III were used to create ternary regression models from two different data sets, which were then compared. One ternary study was designed to focus on low content analysis, while the other was designed to focus on whole content analysis. The ternary system that gave the best results was then used to monitor the solid state transformations of forms I and III to the amorphous phase during cryo-milling.en_US
dc.subjectNear Infrared Spectroscopyen_US
dc.subjectInfrared Spectroscopyen_US
dc.subjectATR IRen_US
dc.subjectX-Ray Powder Diffractionen_US
dc.subjectQuantitative Analysisen_US
dc.subjectPharmaceutical analysisen_US
dc.subjectMultivariate analysisen_US
dc.titleQuantitative Analysis of the Amorphous Phase and Multiple Polymorphs of Model Sulfa-Drugs; Sulfamerazine and Sulfathiazoleen_US
dc.contributor.funderSolid State Pharmaceutical Cluster (SSPC) as part of Science Foundation Ireland (SFI)en_US
dc.local.noteMechanical stress has shown to change the solid state of many pharmaceuticals, changing its physical behaviour. This research prepared different solid states of two model compounds, sulfathiazole and sulfamerazine, and created a computational method to quantify any changes that occur to these drugs during milling at room temperature and cryo-temperatures.en_US

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